Androgens raise venous and arterial adrenergic tone.

Summary

Principal Investigator: Doug S Martin
Abstract: The development of hypertension is sexually dimorphic. Blood pressure rises more quickly and to a greater extent in males. While considerable research attention has been directed toward the arterial circulation, there has been relatively little investigation of venous changes in hypertension. Our previous work indicated that venous tone was elevated by neural mechanisms in the developmental stages of hypertension in the spontaneously hypertensive rat, an animal model of that resembles essential hypertension in humans. Recent data suggest that veins and arteries are affected differently by hypertension. Thus, this project will test the general hypothesis that androgens amplify adrenergic tone of the arterial and venous vascular compartments via different mechanisms. Specific aim I will address the possibility that this effect occurs at the level of vascular smooth muscle. Specific aim II will assess the role of changes in norepinephrine release mechanisms. Specific aim III will investigate the effects of androgens on CNS mechanisms controlling sympathetic nervous system outflow from the hypothalamus. Functional studies will be conducted in vivo and in isolated perfused vascular beds. Androgen induced changes in protein and gene expression will be assessed with Western blot and real time RT-PCR approaches. Collectively we expect these studies to show that androgens amplify adrenergic tone in veins and arteries but that the underlying mechanisms are different in these two vascular compartments. These data will expand our understanding of sex steroid modulation of vascular function and of hypertension development. Hypertension is a significant public health problem that is a risk factor for many other cardiovascular diseases. In addition, in patients hypertension is poorly controlled. Moreover, postural hypotension is common adverse effect of antihypertensive therapy, implying dysregulation of venous function. A better understanding the factors that control arterial and venous tone in hypertension may lead to design antihypertensive drugs with fewer adverse effects
Funding Period: ----------------2000 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Androgens potentiate renal vascular responses to angiotensin II via amplification of the Rho kinase signaling pathway
    Jin Song
    Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA
    Cardiovasc Res 72:456-63. 2006
  2. pmc The effects of estrogen and testosterone on gene expression in the rat mesenteric arteries
    Kathleen M Eyster
    Division of Basic Biomedical Science, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA
    Vascul Pharmacol 47:238-47. 2007
  3. ncbi Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed
    Connie J Mark
    Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA
    Am J Physiol Regul Integr Comp Physiol 293:R1969-75. 2007
  4. pmc Bortezomib, a proteasome inhibitor, attenuates angiotensin II-induced hypertension and aortic remodeling in rats
    Shuai Li
    Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, United States of America
    PLoS ONE 8:e78564. 2013
  5. pmc Involvement of protein kinase C-CPI-17 in androgen modulation of angiotensin II-renal vasoconstriction
    Jin Song
    Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA
    Cardiovasc Res 85:614-21. 2010
  6. pmc Blood pressure and mesenteric vascular reactivity in spontaneously hypertensive rats 7 months after gonadectomy
    Rabelais Tatchum-Talom
    UPMC McKeesport Family Medicine, McKeesport, PA, USA
    J Cardiovasc Pharmacol 57:357-64. 2011
  7. pmc Estrogens and selective estrogen receptor modulators regulate gene and protein expression in the mesenteric arteries
    Connie J Mark-Kappeler
    Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, SD 57069, USA
    Vascul Pharmacol 55:42-9. 2011

Detail Information

Publications7

  1. ncbi Androgens potentiate renal vascular responses to angiotensin II via amplification of the Rho kinase signaling pathway
    Jin Song
    Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA
    Cardiovasc Res 72:456-63. 2006
    ..This study assessed whether the Rho kinase signaling pathway contributes to androgenic amplification of angiotensin II (Ang II) induced pressor and renal constrictor responses...
  2. pmc The effects of estrogen and testosterone on gene expression in the rat mesenteric arteries
    Kathleen M Eyster
    Division of Basic Biomedical Science, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA
    Vascul Pharmacol 47:238-47. 2007
    ..Aryl hydrocarbon nuclear translocator-like gene was reduced by testosterone. These data identify genes not previously known to be responsive to estrogen and testosterone in the vasculature...
  3. ncbi Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed
    Connie J Mark
    Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA
    Am J Physiol Regul Integr Comp Physiol 293:R1969-75. 2007
    ..However, the three formulations of estrogen did not produce equivalent effects, and the effects of the SERMs were different from those of the estrogens...
  4. pmc Bortezomib, a proteasome inhibitor, attenuates angiotensin II-induced hypertension and aortic remodeling in rats
    Shuai Li
    Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, United States of America
    PLoS ONE 8:e78564. 2013
    ..This study tested the hypothesis that the proteasome inhibitor, bortezomib, would attenuate AngII-induced hypertension and its sequelae such as aortic remodeling in rats...
  5. pmc Involvement of protein kinase C-CPI-17 in androgen modulation of angiotensin II-renal vasoconstriction
    Jin Song
    Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA
    Cardiovasc Res 85:614-21. 2010
    ..We tested the hypothesis that this pathway may contribute to androgenic amplification of Ang II-renal vasoconstriction in the New Zealand genetically hypertensive (NZGH) rat...
  6. pmc Blood pressure and mesenteric vascular reactivity in spontaneously hypertensive rats 7 months after gonadectomy
    Rabelais Tatchum-Talom
    UPMC McKeesport Family Medicine, McKeesport, PA, USA
    J Cardiovasc Pharmacol 57:357-64. 2011
    ..We tested the hypothesis that long-term loss of sex steroids promotes changes in mesenteric vascular reactivity that impact the maintenance of hypertension in the spontaneously hypertensive rats (SHR)...
  7. pmc Estrogens and selective estrogen receptor modulators regulate gene and protein expression in the mesenteric arteries
    Connie J Mark-Kappeler
    Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, SD 57069, USA
    Vascul Pharmacol 55:42-9. 2011
    ..Consequently, the use of these agents may be associated with a unique profile of functional and structural changes in the mesenteric arterial circulation...